Targeted inhibition of β-catenin by miR-320 and decreased MMP-13 expression in suppressing chondrocyte collagen degradation

H.-X. Zhang, C. Sun, H.-C. Yu, B. Song, Z.-X. Pan

Department of Joint Surgery, The No. 89 Hospital of the People’s Liberation Army of China, Weifang, Shandong, China. b09473162167358@sina.com

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• Orthopedics

OBJECTIVE: Wnt/β-catenin pathway plays a critical role in modulating embryonic development, cell growth, and differentiation. The over-expression of β-catenin activates this pathway and up-regulates expression of matrix metalloproteinase-13 (MMP-13), and promotes matrix degradation and occurrence of osteoarthritis (OA). This study aims to explore the effect of miR-320 expression in OA chondrocyte and underlying mechanisms.

PATIENTS AND METHODS: Chondrocyte tissues from OA patients and normal individuals were collected for the detection of expression levels of miR-320, β-catenin, MMP-13, and alpha-1 chain of type II collagen (COL2A1). Dual luciferase reporter assay was performed to test targeted regulation between miR-320 and β-catenin. IL-1β was used to simulate in vitro cultured chondrocytes, which were transfected with miR-320 mimic and/or si-β-catenin, followed by quantification of miR-320, β-catenin, MMP-13, and COL2A1.

RESULTS: In chondrocytes of OA patients, expression of microRNA (miR)-320 is decreased. Bioinformatics analysis revealed complementary binding sites between miR-320 and β-catenin. Compared to control group, increasing levels of β-catenin and MMP-13 expression with reduction of miR-320 and COL2A1 expressions were observed in OA chondrocytes. Transfection of miR-320 mimic and/or si-β-catenin depressed expression of β-catenin and MMP-13 inside chondrocytes, accompanied with elevation of COL2A1 expression.

CONCLUSIONS: MiR-320 expression in OA chondrocyte is decreased, accompanied with up regulation of β-catenin and MMP-13. MiR-320 can inhibit β-catenin and MMP-13 expressions, elevates COL2A1 expression, which provides novel insights for the treatment of osteoarthritis.

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